Randomized trial evidence suggests that treatment with dabigatran etexilate (Pradaxa, Boehringer Ingelheim) raises the risk of gastrointestinal (GI) bleeding compared with treatment with warfarin, suggests a meta-analysis, with findings entirely opposite those of a recent analysis of dabigatran and warfarin use in the FDA Mini-Sentinel database by several employees of the agency....

In the new meta-analysis of four [Pradaxa (dabigatran)] trials with enough available GI-bleed data, the risk of such events was raised 41% (p<0.001) with the new oral direct thrombin inhibitor compared with the vintage vitamin-K antagonist. The risk increase persisted after dropping any one trial from the meta-analysis, including the RE-LY trial, which overwhelmingly contributed the most patients and events, according to the authors, led by Dr Ilke Sipahi (University Hospitals and Case Medical Center, Cleveland, OH).

The RE-LY trial is well known to have shown more GI bleeds with [Pradaxa (dabigatran)], while intracranial hemorrhage was more common with warfarin (p<0.001 for both differences).

The increased GI-bleed risk in the meta-analysis contrasts with the 54% risk reduction seen for [Pradaxa (dabigatran)] vs warfarin in the Mini-Sentinel data, taken from electronic health records routinely monitored by the FDA covering a 14-month period ending at the close of 2011. But that analysis, recently published in the New England Journal of Medicine and reported then by heartwire , didn't adjust for potential confounders....

Sipahi agreed that a "healthy-user bias," including a lesser prevalence of renal dysfunction, may underlie the apparent GI-bleeding risk reduction with [Pradaxa (dabigatran)] in the Mini-Sentinel analysis.

We will continue to monitor the medical journals for developments as regards the association between Pradaxa and gastrointestinal (GI) bleeding events, some of which have caused patient deaths.

Randomized trial evidence suggests that treatment with dabigatran etexilate (Pradaxa, Boehringer Ingelheim) raises the risk of gastrointestinal (GI) bleeding compared with treatment with warfarin, suggests a meta-analysis, with findings entirely opposite those of a recent analysis of dabigatran and warfarin use in the FDA Mini-Sentinel database by several employees of the agency....

In the new meta-analysis of four [Pradaxa (dabigatran)] trials with enough available GI-bleed data, the risk of such events was raised 41% (p<0.001) with the new oral direct thrombin inhibitor compared with the vintage vitamin-K antagonist. The risk increase persisted after dropping any one trial from the meta-analysis, including the RE-LY trial, which overwhelmingly contributed the most patients and events, according to the authors, led by Dr Ilke Sipahi (University Hospitals and Case Medical Center, Cleveland, OH).

The RE-LY trial is well known to have shown more GI bleeds with [Pradaxa (dabigatran)], while intracranial hemorrhage was more common with warfarin (p<0.001 for both differences).

The increased GI-bleed risk in the meta-analysis contrasts with the 54% risk reduction seen for [Pradaxa (dabigatran)] vs warfarin in the Mini-Sentinel data, taken from electronic health records routinely monitored by the FDA covering a 14-month period ending at the close of 2011. But that analysis, recently published in the New England Journal of Medicine and reported then by heartwire , didn't adjust for potential confounders....

Sipahi agreed that a "healthy-user bias," including a lesser prevalence of renal dysfunction, may underlie the apparent GI-bleeding risk reduction with [Pradaxa (dabigatran)] in the Mini-Sentinel analysis.

We will continue to monitor the medical journals for developments as regards the association between Pradaxa and gastrointestinal (GI) bleeding events, some of which have caused patient deaths.